Bovine major histocompatibility complex (BoLA) heterozygote advantage against the outcome of bovine leukemia virus infection.

Bovine leukemia virus (BLV) causes enzootic bovine leucosis. Host genetic heterozygosity at the major histocompatibility complex can enhance the ability to combat infectious diseases. However, heterozygote advantage is loci specific and depends on disease type. Bovine leukocyte antigen (BoLA)-DRB3 polymorphisms are related with BLV-infection outcome; however, whether BoLA-DRB3 heterozygotes have an advantage against BLV-induced lymphoma and proviral load (PVL) remains unclear. By analyzing 1567 BLV-infected individuals, we found that BoLA-DRB3 heterozygous status was significantly associated with lymphoma resistance irrespective of cattle breeds (p < 0.0001). Similarly, decreased PVL was observed in BoLA-DRB3 heterozygotes (p = 0.0407 for Holstein cows; p = 0.0889 for Japanese Black cattle). Our report provides first evidence of BoLA-DRB3 heterozygote advantage against BLV infection outcome.